The objective is to further elucidate role of transforming growth factor beta (TGF beta) signaling in tumor progression at the molecular, cellular and in vivo levels. Based on previously published studies and preliminary data, we hypothesize that disruption of TGF signaling in stromal cells impairs normal stromal:epithelial interactions and contributes to tumor progression. We will address this hypothesis by: 1) determining the molecular and cellular mechanisms of TGF beta signaling in stromal:epithelial interactions and 2) determining the role of stromal cell specific TGF beta signaling in mammary tumor progression and metastases. Aberrant expression or activity of TGF beta or receptors type I and type II have been linked to in vivo tumor models exhibiting metastatic phenotypes and to human breast cancer cells. Our research will address the function and mechanisms through which stromal cell specific TGF beta signaling specifically contributes to tumor progression, and will further contribute to the understanding and development of anti tumor therapies.